Structure-activity relationship studies of the two-component lantibiotic haloduracin.
The lantibiotic haloduracin consists of two posttranslationally processed peptides, Halalpha and Halbeta, which act in synergy to provide bactericidal activity. An in vitro haloduracin production system was used to examine the biological impact of disrupting individual thioether rings in each peptide. Surprisingly, the Halalpha B ring, which contains a highly conserved CTLTXEC motif, was expendable. This motif has been proposed to interact with haloduracin's predicted target, lipid II. Exchange of the glutamate residue in this motif for alanine or glutamine completely abolished antibacterial activity. This study also established that Halalpha-Ser26 and Halbeta-Ser22 escape dehydration, requiring revision of the Halbeta structure previously proposed. Extracellular proteases secreted by the producer strain can remove the leader peptide, and the Halalpha cystine that is dispensable for bioactivity protects Halalpha from further proteolytic degradation.
Cooper
Lisa E
LE
Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
McClerren
Amanda L
AL
Chary
Anita
A
van der Donk
Wilfred A
WA
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001407:Bacillus / Q000737:chemistry / Q000378:metabolism; D001430:Bacteriocins / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010447:Peptide Hydrolases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013440:Sulfides / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D013440:Sulfides; C515824:haloduracin, Bacillus halodurans; D010447:Peptide Hydrolases